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The use of proteomics in human studies investigating stroke and myocardial infarction (MI) has been increasing, prompting a review of the literature. This revealed proteinaceous biomarkers of stroke from thrombi, brain tissue, cells, and particles, some of which cross the blood-brain barrier (BBB). Several proteins were also implicated in coronary artery disease (CAD), which often underlies MI, cholesterol transportation, and inflammation. Furthermore, the platelet proteome revealed itself as a potential therapeutic target, along with differentially expressed proteins associated with MI progression. Moreover, proteomic data enhanced the performance of conventional risk scores and causal protein discovery has improved interventions and drug development for patients with MI and other conditions. These findings suggest that proteomics holds much promise for future stroke and MI research., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Circulating plasma proteins play key roles in human health and can potentially be used to measure biological age, allowing risk prediction for age-related diseases, multimorbidity and mortality. Here we developed a proteomic age clock in the UK Biobank (n = 45,441) using a proteomic platform comprising 2,897 plasma proteins and explored its utility to predict major disease morbidity and mortality in diverse populations. We identified 204 proteins that accurately predict chronological age (Pearson r = 0.94) and found that proteomic aging was associated with the incidence of 18 major chronic diseases (including diseases of the heart, liver, kidney and lung, diabetes, neurodegeneration and cancer), as well as with multimorbidity and all-cause mortality risk. Proteomic aging was also associated with age-related measures of biological, physical and cognitive function, including telomere length, frailty index and reaction time. Proteins contributing most substantially to the proteomic age clock are involved in numerous biological functions, including extracellular matrix interactions, immune response and inflammation, hormone regulation and reproduction, neuronal structure and function and development and differentiation. In a validation study involving biobanks in China (n = 3,977) and Finland (n = 1,990), the proteomic age clock showed similar age prediction accuracy (Pearson r = 0.92 and r = 0.94, respectively) compared to its performance in the UK Biobank. Our results demonstrate that proteomic aging involves proteins spanning multiple functional categories and can be used to predict age-related functional status, multimorbidity and mortality risk across geographically and genetically diverse populations., (© 2024. The Author(s).)

Furin is an important proteolytic enzyme, converting several proteins from inactive precursors to their active forms. Recently, proteo-genomic analyses in European and East Asian populations suggested a causal association of furin with ischaemic heart disease, and there is growing interest in its role in cardiovascular disease (CVD) aetiology. In this narrative review, we present a critical appraisal of evidence from population studies to assess furin's role in CVD risk and potential as a drug target for CVD. Whilst most observational studies report positive associations between furin expression and CVD risk, some studies report opposing effects, which may reflect the complex biological roles of furin and its substrates. Genetic variation in FURIN is also associated with CVD and its risk factors. We found no evidence of current clinical development of furin as a drug target for CVD, although several phase 1 and 2 clinical trials of furin inhibitors as a type of cancer immunotherapy have been completed. The growing field of proteo-genomics in large-scale population studies may inform the future development of furin and other potential drug targets to improve the treatment and prevention of CVD.

Context: Postprandial lipemia (PPL) is associated with increased risk of endothelial dysfunction (ED), a precursor of atherosclerotic cardiovascular disease (ASCVD). The effects of low-carbohydrate, high-fat (LCHF) diets on ASCVD risk are uncertain; therefore, gaining a greater understanding of LCHF meals on PPL may provide valuable insights., Objective: The current systematic review investigated the effects of single LCHF meal consumption on PPL and markers of ED., Data Sources: CINAHL Plus, PubMed, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for key terms related to endothelial function, cardiovascular disease, glycemia, lipemia, and the postprandial state with no restriction on date., Data Extraction: Full-text articles were independently screened by 2 reviewers, of which 16 studies were eligible to be included in the current review. All trials reported a minimum analysis of postprandial triglycerides (PPTG) following consumption of an LCHF meal (<26% of energy as carbohydrate). Results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement., Data Analysis: Single-meal macronutrient composition was found to play a key role in determining postprandial lipid and lipoprotein responses up to 8 hours post-meal. Consumption of LCHF meals increased PPTG and may contribute to ED via reduced flow-mediated dilation and increased oxidative stress; however, energy and macronutrient composition varied considerably between studies., Conclusion: Consumption of an LCHF meal had a negative impact on PPL based on some, but not all, single-meal studies; therefore, the contribution of LCHF meals to cardiometabolic health outcomes remains unclear. Further research is needed on specific categories of LCHF diets to establish a causal relationship between postprandial modulation of lipids/lipoproteins and impaired vascular endothelial function., Systematic Review Registration: PROSPERO registration no. CRD 42023398774., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Objective: Integrated analyses of plasma proteomics and genetic data in prospective studies can help assess the causal relevance of proteins, improve risk prediction, and discover novel protein drug targets for type 2 diabetes (T2D)., Research Design and Methods: We measured plasma levels of 2,923 proteins using Olink Explore among ∼2,000 randomly selected participants from China Kadoorie Biobank (CKB) without prior diabetes at baseline. Cox regression assessed associations of individual protein with incident T2D (n = 92 cases). Proteomic-based risk models were developed with discrimination, calibration, reclassification assessed using area under the curve (AUC), calibration plots, and net reclassification index (NRI), respectively. Two-sample Mendelian randomization (MR) analyses using cis-protein quantitative trait loci identified in a genome-wide association study of CKB and UK Biobank for specific proteins were conducted to assess their causal relevance for T2D, along with colocalization analyses to examine shared causal variants between proteins and T2D., Results: Overall, 33 proteins were significantly associated (false discovery rate <0.05) with risk of incident T2D, including IGFBP1, GHR, and amylase. The addition of these 33 proteins to a conventional risk prediction model improved AUC from 0.77 (0.73-0.82) to 0.88 (0.85-0.91) and NRI by 38%, with predicted risks well calibrated with observed risks. MR analyses provided support for the causal relevance for T2D of ENTR1, LPL, and PON3, with replication of ENTR1 and LPL in Europeans using different genetic instruments. Moreover, colocalization analyses showed strong evidence (pH4 > 0.6) of shared genetic variants of LPL and PON3 with T2D., Conclusions: Proteomic analyses in Chinese adults identified novel associations of multiple proteins with T2D with strong genetic evidence supporting their causal relevance and potential as novel drug targets for prevention and treatment of T2D., (© 2024 by the American Diabetes Association.)

The current study aimed to evaluate the psychometric properties of the Difficulties in Emotion Regulation Scale-Short Form (DERS-SF) in Iran, including testing its measurement invariance across sexes, as well as community and student populations. Two samples were recruited: a community sample of 583 participants (58.7% female; M age = 33.55) and a university student sample of 409 participants (67.2% female; M age = 24.48). Besides the DERS-SF, participants completed a battery of instruments online, measuring mentalizing capacity and borderline personality features. Confirmatory factor analyses supported the tenability of the five-factor model, excluding the awareness subscale. Except for the awareness subscale, acceptable to excellent internal consistencies were found for the DERS-SF and its subscales. The awareness-excluded DERS-SF was significantly and strongly associated with relevant constructs (|r s | = .49 to .59). This study also found evidence for configural, metric, and scalar invariance of the DERS-SF across sexes and community and student populations. Our findings extended the evidence for the validity and reliability of the DERS-SF and its awareness-excluded version by administering it in Iranian samples and supporting its cross-cultural applicability.

Objective: High-fat diets cause obesity in male mice; however, the underlying mechanisms remain controversial. Here, three contrasting ideas were assessed: hedonic overdrive, reverse causality, and passive overconsumption models., Methods: A total of 12 groups of 20 individually housed 12-week-old C57BL/6 male mice were exposed to 12 high-fat diets with varying fat content from 40% to 80% (by calories), protein content from 5% to 30%, and carbohydrate content from 8.4% to 40%. Body weight and food intake were monitored for 30 days after 7 days at baseline on a standard low-fat diet., Results: After exposure to the diets, energy intake increased first, and body weight followed later. Intake then declined. The peak energy intake was dependent on both dietary protein and carbohydrate, but not the dietary fat and energy density, whereas the rate of decrease in intake was only related to dietary protein. On high-fat diets, the weight of food intake declined, but despite this average reduction of 14.4 g in food intake, they consumed, on average, 357 kJ more energy than at baseline., Conclusions: The hedonic overdrive model fit the data best. The other two models were not supported., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)

Aims: Reduced muscle mass and reduced strength are frequently associated with both alterations in blood lipids and poorer cardiometabolic outcomes in epidemiological studies; however, a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association of genetically determined appendicular lean mass (ALM) and handgrip strength (HGS) with serum lipid particle diameter., Methods and Results: Mendelian randomization was implemented using summary-level data from the largest genome-wide association studies on ALM ( n = 450 243), HGS ( n = 223 315), and lipoprotein [low-density lipoprotein (LDL), very LDL (VLDL), and high-density lipoprotein (HDL)] particle diameters ( n = 115 078). Inverse variance-weighted (IVW) method was used to calculate the causal estimates. Weighted median-based method, MR-Egger, and leave-one-out method were applied as sensitivity analysis. Greater ALM had a statistically significant positive effect on HDL particle diameter (MR-Egger: β = 0.055, SE = 0.031, P = 0.081; IVW: β = 0.068, SE = 0.014, P < 0.001) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β = -0.114, SE = 0.039, P = 0.003; IVW: β = -0.081, SE = 0.017, P < 0.001). Similarly, greater HGS had a statistically significant positive effect on HDL particle diameter (MR-Egger: β = 0.433, SE = 0.184, P = 0.019; IVW: β = 0.121, SE = 0.052, P = 0.021) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β = -0.416, SE = 0.163, P = 0.011; IVW: β = -0.122, SE = 0.046, P = 0.009). There was no statistically significant effect of either ALM or HGS on LDL particle diameter., Conclusion: There were potentially causal associations between both increasing ALM and HGS and increasing HDL particle size and decreasing VLDL particle size. These causal associations may offer possibilities for interventions aimed at improving cardiovascular disease risk profile., Competing Interests: Conflict of interest: R.K. has received payments from Abbott for the creation of educational media content, as well as speaker fees. All other authors declare that they have no relevant conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Dietary nitrates are thought to confer several cardiometabolic health benefits, including improvements in blood pressure and the plasma lipid profile. However, existing data from Iran is conflicting and there is a dearth of literature focusing on non-adult populations. A total of 988 adolescent girls were recruited from schools in different areas of Mashhad and Sabzevar, Iran. Dietary nitrate intake was assessed using a food frequency questionnaire and participants were categorized into quartiles based on this. Differences in participant characteristics between quartiles were assessed using one-way ANOVA and associations between total nitrate intake, nitrate intake from vegetables and cardiometabolic risk markers (blood lipid profile, fasting blood glucose, systolic and diastolic blood pressure) were assessed using linear regression. Nitrate intake from vegetables was positively correlated with triglycerides, even after adjusting for several variables (β = 0.086, 95% CI = 0.002-0.097; P = 0.043). Total nitrate intake was also significantly positively associated with serum triglycerides (β = 0.097, 95% CI = 0.010-0.084; P = 0.012); however, this relationship disappeared after adjusting for several variables. Significant interaction effects were observed between total nitrate intake, nitrate intake from vegetables, and vitamin C upon triglycerides (P < 0.01). No significant relationships were found between total nitrate intake, nitrate intake from vegetables, and other cardiometabolic risk markers. Our findings suggest there may be neutral or possibly detrimental cardiovascular effects of dietary nitrate and/or vitamin C intake which are not in agreement with contemporary literature and warrant further investigation., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Context: Nonalcoholic fatty liver disease (NAFLD) is prevalent in 25-30% of British and European populations, representing a potential global public health crisis. Marine omega-3 (n-3) polyunsaturated fatty acids offer well-evidenced benefits to NAFLD biomarkers; however, the effect of plant-based n-3 has not been evaluated with a systematic review and meta-analysis., Objective: The review aimed to systematically evaluate the effect of plant-based n-3 supplementation on NAFLD surrogate biomarkers and parameters., Data Sources: Medline (EBSCO), PubMed, CINAHL (EBSCO), Cochrane Central Register of Controlled Trials, the International Clinical Trials Registry Platform, and Google Scholar databases were searched to identify randomized controlled trials published between January 1970 and March 2022 evaluating the impact of plant-based n-3 interventions on diagnosed NAFLD. The review followed the PRISMA checklist and is PROSPERO registered (CRD42021251980)., Data Extraction: A random-effects model and generic inverse variance methods synthesized quantitative data, followed by a leave-one-out method for sensitivity analysis. We identified 986 articles; after the application of selection criteria, six studies remained with 362 patients with NAFLD., Results: The meta-analysis showed that plant-based n-3 fatty acid supplementation significantly reduced alanine aminotransferase (ALT) (mean difference: 8.04 IU/L; 95% confidence interval: 14.70, 1.38; I2 = 48.61%) and plasma/serum triglycerides (44.51 mg/dL; 95% confidence interval: -76.93, -12.08; I2 = 69.93%), alongside body-composition markers in patients with NAFLD (P < 0.05)., Conclusion: Plant-based n-3 fatty acid supplementation improves ALT enzyme biomarkers, triglycerides, body mass index, waist circumference, and weight loss when combined with lifestyle interventions to increase physical activity and a calorie-controlled diet. Further research is needed to identify the most effective plant-based n-3 sources in larger numbers of patients with NAFLD over longer study durations., Systematic Review Registration: PROSPERO registration no. CRD42021251980., (© The Author(s) 2023. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Early life nutrition can reprogram development and exert long-term consequences on body weight regulation. In mice, maternal high-fat diet (HFD) during lactation predisposed male but not female offspring to diet-induced obesity when adult. Molecular and cellular changes in the hypothalamus at important time points are examined in the early postnatal life in relation to maternal diet and demonstrated sex-differential hypothalamic reprogramming. Maternal HFD in lactation decreased the neurotropic development of neurons formed at the embryo stage (e12.5) and impaired early postnatal neurogenesis in the hypothalamic regions of both males and females. Males show a larger increased ratio of Neuropeptide Y (NPY) to Pro-opiomelanocortin (POMC) neurons in early postnatal neurogenesis, in response to maternal HFD, setting an obese tone for male offspring. These data provide insights into the mechanisms by which hypothalamic reprograming by early life overnutrition contributes to the sex-dependent susceptibility to obesity in adult life in mice., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Adolescence is a key time for the development of depression symptoms and the diet quality may be associated with mental health conditions. The present study examined the association between depression and quality of life (QoL) and the global diet quality score (GDQS) as a simple and standardized metric diet quality in Iranian adolescents., Methods: This cross-sectional study was conducted on 733 adolescent girls recruited using a random cluster sampling method. A 147-item food frequency questionnaire (FFQ) was used for dietary intake assessment. The GDQS is gained by summing points of all the 25 food groups, ranged from 0 to 49. Depression symptoms were assessed using a Persian version of the Beck Depression Inventory (BDI). For assessment of health-related QoL, the Short Form 12 Survey-version 2 (SF-12v2) questionnaire was employed. Multivariable logistic regression examined the association of depression and QoL with GDQS in crude and adjusted models., Results: Adolescent girls in the highest tertile of GDQS score compared with the lowest tertile had a 41% lower odds of depressive symptoms (OR: 0.59; 95% CI: 0.39-0.90, P = 0.01). The participants in the third tertile of GDQS score had lower odds of poor QoL compared with the first tertile (OR: 0.56; 95% CI: 0.37-0.85, P < 0.01). These associations remained significant (both P = 0.01) after adjustment for age, energy intake, body mass index (BMI), physical activity, and menstruation (depressive symptoms: OR: 0.59; 95% CI: 0.38-0.92; QoL: OR: 0.59; 95% CI: 0.38-0.91, P = 0.01)., Conclusion: We found that adolescent girls with a higher score of the GDQS had lower odds of depression and poor QoL Prospective and interventional investigations are needed to reach a clear vision., (© 2023. The Author(s).)

Adiposity is associated with multiple diseases and traits, but little is known about the causal relevance and mechanisms underlying these associations. Large-scale proteomic profiling, especially when integrated with genetic data, can clarify mechanisms linking adiposity with disease outcomes. We examined the associations of adiposity with plasma levels of 1463 proteins in 3977 Chinese adults, using measured and genetically-instrumented BMI. We further used two-sample bi-directional MR analyses to assess if certain proteins influenced adiposity, along with other (e.g. enrichment) analyses to clarify possible mechanisms underlying the observed associations. Overall, the mean (SD) baseline BMI was 23.9 (3.3) kg/m 2 , with only 6% being obese (i.e. BMI ≥ 30 kg/m 2 ). Measured and genetically-instrumented BMI was significantly associated at FDR < 0.05 with levels of 1096 (positive/inverse: 826/270) and 307 (positive/inverse: 270/37) proteins, respectively, with FABP4, LEP, IL1RN, LSP1, GOLM2, TNFRSF6B, and ADAMTS15 showing the strongest positive and PON3, NCAN, LEPR, IGFBP2 and MOG showing the strongest inverse genetic associations. These associations were largely linear, in adiposity-to-protein direction, and replicated (> 90%) in Europeans of UKB (mean BMI 27.4 kg/m 2 ). Enrichment analyses of the top > 50 BMI-associated proteins demonstrated their involvement in atherosclerosis, lipid metabolism, tumour progression and inflammation. Two-sample bi-directional MR analyses using cis-pQTLs identified in CKB GWAS found eight proteins (ITIH3, LRP11, SCAMP3, NUDT5, OGN, EFEMP1, TXNDC15, PRDX6) significantly affect levels of BMI, with NUDT5 also showing bi-directional association. The findings among relatively lean Chinese adults identified novel pathways by which adiposity may increase disease risks and novel potential targets for treatment of obesity and obesity-related diseases., (© 2023. The Author(s).)

Background and Aims: According to the NOVA classification system, ultra-processed foods result from extensive industrial processing and use ingredients derived from food and non-food products, which can negatively impact on cardiovascular disease risk factors. Despite this, few studies have investigated UPFs in Middle Eastern populations regardless of high consumption in this region., Methods and Results: This cross-sectional study was conducted on data from the Prospective Epidemiological Research Studies in Iran Kharemeh cohort (n = 6611). Food frequency questionnaires were assessed and the ratio of total UPFs energy/total energy intake was calculated. Data was categorized into tertiles of UPF consumption using the NOVA classification system. Kruskal-Wallis tests were used to assess differences in nutrient and food intakes between tertiles and logistic regression analysis was applied to assess the associations between UPFs and CVD risk factors. After adjustment for potential confounders the logistic regression analysis revealed significant positive relationships between intakes of UPFs and waist circumference (WC) (T 2 : OR; 1.34, 95% CI; 1.13-1.60 - T 3 : OR; 1.41, 95% CI; 1.18-1.69, P ˂0.001), low-density lipoprotein cholesterol (LDL-C) (T 2 : OR; 1.20, 95% CI; 1.05-1.37 - T 3 : OR; 1.27, 95% CI; 1.11-1.45, P ˂0.001), non-high-density lipoprotein cholesterol (non-HDL) (T 2 : OR; 1.21, 95% CI; 1.07-1.37 - T 3 : OR; 1.24, 95% CI; 1.10-1.41, P ˂0.001) and LDL-C to HDL-C ratio (T 2 : OR; 1.15, 95% CI; 1.02-1.31 - T 3 : OR; 1.21, 95% CI; 1.07-1.38, P = 0.002)., Conclusion: The consumption of UPFs was positively associated with WC and atherogenic blood lipids. However, increased intakes of fiber and unsaturated fats were also found in those consuming more UPFs, which was not expected. These findings offer insights into an understudied population and warrant further research., Competing Interests: Declaration of competing interest All authors declare that they have no conflict of interest., (Copyright © 2023. Published by Elsevier B.V.)

We used an established mediation analysis to investigate the role of adiposity in the relation between serum 25(OH)D with markers of inflammation and glucose and insulin metabolism. We used data from National Health and Nutrition Examination Survey (2005-2010), to evaluate the associations between serum 25(OH)D and markers of insulin resistance (IR) or inflammation, and whether these associations are mediated by adiposity factors. Analysis of co-variance and conceptual causal mediation analysis were conducted taking into consideration the survey design and sample weights. BMI was found to have significant mediation effects (to varied extent) on the associations between serum 25(OH)D and CRP, apo-B, fasting glucose, insulin, HOMA-IR, HOMA-B and HbA1c (all P < 0·05). Both WC and apVAT were also found to partly mediate the associations between serum 25 25(OH)D with CRP, FBG, HbA1c, TAG and HDL-cholesterol (all P < 0·05). These findings support the importance of optimising 25(OH)D status in conditions with abnormal adiposity (i.e. obesity) and treatments for the prevention of cardiometabolic diseases affecting adipose tissue metabolism (i.e. weight loss).

Objective: Observational studies have evaluated the relationships among plasma short chain fatty acids (SCFA) produced by gut microbiota, renal function, and risk of chronic kidney disease (CKD). In the present study, Mendelian Randomization (MR) analysis was applied to obtain unconfounded estimates of the casual association of genetically determined plasma valerate (an SCFA) with kidney function and risk of CKD., Method: MR was performed by using summary-level data from the largest genome-wide association studies (GWAS) conducted on plasma valerate, CKD, and estimated glomerular filtration rate (eGFR; separately in diabetic and nondiabetic individuals). Inverse variance weighted method (IVW), weighted median-based method, MR-Egger, as well as MR-Pleiotropy RESidual Sum and Outlier (PRESSO) were applied. Sensitivity analysis was conducted using the leave-one-out method., Results: No significant association was observed between plasma valerate and CKD (IVW: β = 0.234, p  = 0.744). In contrast, plasma valerate was positively associated with eGFR in the total population (IVW: β = 0.049, p  = 0.022) and among nondiabetic individuals (IVW: β = 0.058, p  = 0.009), but not in the diabetic population (IVW: β = -0.052, p  = 0.603). None of the estimated associations was subjected to significant level of heterogeneity. Furthermore, MR-PRESSO analysis did not show any chance of outlier for all estimates. The pleiotropy test, with very a negligible intercept and insignificant p value, also indicated no chance of pleiotropy for all of our estimations (all p  > 0.539). The results of the MR-Robust Adjusted Profile Score were identical with the IVW estimates, highlighting again no possibility of pleiotropy. Results of the leave-one-out method demonstrated that the links were not driven by single-nucleotide polymorphisms., Conclusions: Individuals with higher plasma valerate levels had better renal function, defined by eGFR. This finding was observed in the total population and in nondiabetic subjects, but not in those with diabetes. Further research is needed to elucidate the links among plasma valerate, kidney function, and CKD.

Objective: To investigate the association between plasma trans fatty acids (TFAs) and bone mineral density (BMD) and risk of fracture among US adults. Furthermore, we have evaluated the impact of inflammation on this relationship., Methods: Participants (the National Health and Nutrition Examination Survey) with measured data on BMD and TFAs were included. TFAs were measured by gas chromatography-mass spectrometry and BMD was measured using dual-energy x-ray absorptiometry densitometers., Results: Of the 4022 eligible participants, 48.1% were men. The mean age of the population sample was 44.6 years. In the model adjusted for age, sex, race, education, income, physical activity, smoking, fasting blood glucose, systolic and diastolic blood pressure, body mass index, diabetes, and hypertension, across the increasing quartiles (Q) of individual plasma TFAs, BMD decreased for most of the sites measure: for example, Q1 vs. Q4 1.04 vs. 0.095 g/cm 2 for palmitelaidic acid and 1.11 vs. 0.099 g/cm 2 for elaidic acid (all p  < 0.001). In models using the same adjustment, linear regression displayed a significant negative association between plasma TFAs and BMD for most of the sites measured (all p  < 0.001). Moderation analysis revealed that inflammation [assessed as a serum C-reactive protein (CRP)] was not significantly implicated in the relationship between BMD and TFAs. There was no significant difference in percentage of fractures (hip, spine, wrist) observed across quartiles of plasma TFAs (all p  > 0.125)., Conclusions: Our findings highlight, for the first time, the potentially detrimental impact of plasma TFAs on bone health that does not appear to be moderated through inflammation.

Low-carbohydrate high-fat (LCHF) diets can be just as effective as high-carbohydrate, lower-fat (HCLF) diets for improving cardiovascular disease risk markers. Few studies have compared the effects of the UK HCLF dietary guidelines with an LCHF diet on lipids and lipoprotein metabolism using high-throughput NMR spectroscopy. This study aimed to explore the effect of an ad libitum 8-week LCHF diet compared to an HCLF diet on lipids and lipoprotein metabolism and CVD risk factors. For 8 weeks, n = 16 adults were randomly assigned to follow either an LCHF ( n = 8, <50 g CHO p/day) or an HCLF diet ( n = 8). Fasted blood samples at weeks 0, 4, and 8 were collected and analysed for lipids, lipoprotein subclasses, and energy-related metabolism markers via NMR spectroscopy. The LCHF diet increased ( p < 0.05) very small VLDL, IDL, and large HDL cholesterol levels, whereas the HCLF diet increased ( p < 0.05) IDL and large LDL cholesterol levels. Following the LCHF diet alone, triglycerides in VLDL and HDL lipoproteins significantly ( p < 0.05) decreased, and HDL phospholipids significantly ( p < 0.05) increased. Furthermore, the LCHF diet significantly ( p < 0.05) increased the large and small HDL particle concentrations compared to the HCLF diet. In conclusion, the LCHF diet may reduce CVD risk factors by reducing triglyceride-rich lipoproteins and improving HDL functionality.

Background: Little is known regarding health status in an environment characterized by instability and ongoing war risks. This study investigated hypertension disease burden and associations of war-related traumatic events with blood pressure (BP) trajectory over time amongst mid-aged and older Palestinian adults in Gaza Strip., Methods: From nine primary healthcare centers, medical records between 2013 and 2019 were collected for 1,000 mid-aged and older Palestinian adults living in Gaza. Multinomial logistic regression analysis examined associations between war-related traumatic events and BP trajectories derived using latent class trajectory analysis (LCTA)., Results: The prevalence of self-reported injury (of participants or their family members), death of a family member, and violence due to house bombing was 51.4%, 54.1%, and 66.5%, respectively. In total, 22.4% and 21.4% of participants had constant-very-high (CVH) systolic BP (SBP) (>160 mmHg) and diastolic BP (DBP) (>95 mmHg), and normal-stable SBP and DBP was found only 54.9% and 52.6%, respectively. Injury (participants or family members), death of a family member, and violence due to house bombing during wars were associated with CVH SBP with odds ratios [95 CI, OR = 1.79 (1.28-2.48), 1.90 (1.36-2.65), and 1.44 (1.01-2.05)], respectively. The corresponding figures were [95 CI, OR = 1.92 (1.36-2.71), 1.90 (1.35-2.68), and 1.62 (1.13-2.38)] for CVH DBP. Living in debt was positively associated with CVH SBP, [95 CI, OR = 2.49 (1.73-3.60)] and CVH DBP, [95 CI, OR = 2.37 (1.63-3.45)]., Conclusion: The disease burden related to war-related traumatic events is high and positively related to adverse BP trajectory among the mid-aged and older Palestinians living in Gaza. Intervention programs are needed to manage and prevent chronic diseases in this vulnerable population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Jebril, Mazidi, Liu, Baibing, Arafat, Shi and Wang.)

Background: Postprandial metabolomic profiles and their inter-individual variability are not well characterised. Here, we describe postprandial metabolite changes, their correlations with fasting values and their inter- and intra-individual variability, following a standardised meal in the ZOE PREDICT 1 cohort., Methods: In the ZOE PREDICT 1 study ( n = 1002 (NCT03479866)), 250 metabolites, mainly lipids, were measured by a Nightingale NMR panel in fasting and postprandial (4 and 6 h after a 3.7 MJ mixed nutrient meal, with a second 2.2 MJ mixed nutrient meal at 4 h) serum samples. For each metabolite, inter- and intra-individual variability over time was evaluated using linear mixed modelling and intraclass correlation coefficients (ICC) were calculated., Results: Postprandially, 85% (of 250 metabolites) significantly changed from fasting at 6 h (47% increased, 53% decreased; Kruskal-Wallis), with 37 measures increasing by >25% and 14 increasing by >50%. The largest changes were observed in very large lipoprotein particles and ketone bodies. Seventy-one percent of circulating metabolites were strongly correlated (Spearman's rho >0.80) between fasting and postprandial timepoints, and 5% were weakly correlated (rho <0.50). The median ICC of the 250 metabolites was 0.91 (range 0.08-0.99). The lowest ICCs (ICC <0.40, 4% of measures) were found for glucose, pyruvate, ketone bodies (β-hydroxybutyrate, acetoacetate, acetate) and lactate., Conclusions: In this large-scale postprandial metabolomic study, circulating metabolites were highly variable between individuals following sequential mixed meals. Findings suggest that a meal challenge may yield postprandial responses divergent from fasting measures, specifically for glycolysis, essential amino acid, ketone body and lipoprotein size metabolites.

Super-tough poly(lactic acid)/polycarbonate (PLA/PC) (50/50) blends with an excellent balance of stiffness, toughness, and thermal stability were systematically designed and characterized. Poly(methyl methacrylate) (PMMA) was utilized as a novel, highly effective nonreactive interphase to promote PLA-PC phase compatibility. Partial miscibility of PMMA with both PLA and PC produced strong molecular entanglements across the PLA-PC phase boundary followed by an excellent phase adhesion. This was predicted from interfacial energy measurements and supported by dynamic mechanical thermal analysis, morphological observations, and mechanical tests. Ternary PLA/PC/PMMA blends exhibited an exceptional set of stiffness, tensile and flexural strength, tensile and flexural ductility, and thermal stability together with improved impact strength compared with neat PLA and uncompatibilized PLA/PC blends. Addition of nonreactive polybutadiene- g -styrene- co -acrylonitrile (PB- g -SAN) impact modifier to the compatibilized blend resulted in further dramatic improvements in the dispersion state of PC and PMMA phase domains followed by the development of an interconnected structure of PC, PMMA, and PB- g -SAN domains in the PLA matrix. Such a network-like morphology, with rubbery particles percolated at the interface between the dispersed structures and surrounding PLA matrix, produced a tremendous increase in impact resistance (≈700 J/m) and tensile ductility (≈200% strain) while maintaining excellent stiffness (≥2.1 GPa). The combined effects of interfacial localization of impact modifier particles, network-like morphology (extended over the entire volume of the blend), and strong phase interactions between the components (due to mutual miscibility) are described to be responsible for super-tough behavior. The role of PMMA as an efficient interphase adhesion promoter in the toughened quaternary blends is also clarified. Impact fractography revealed multiple void formations, plastic growth of microvoids, and the formation of void-fibrillar structures around as well as inside the dispersed structures as the main micromechanical deformation processes responsible for massive shear yielding and plastic deformation of blends. Blends designed in this work offer remarkable improvements in tensile and flexural ductility, impact resistance, and heat deflection temperature compared with neat PLA resin. The overall characteristics of these blend systems are comparable and/or superior to those of several commercial thermoplastic resins.

Background and Aims: Low-grade inflammation is a mediator of muscle proteostasis. This study aimed to investigate the effects of isolated whey and soy proteins on inflammatory markers., Methods: We conducted a systematic literature search of randomised controlled trials (RCT) through MEDLINE, Web of Science, Scopus and Cochrane Library databases from inception until September 2021. To determine the effectiveness of isolated proteins on circulating levels of C-reactive protein (CRP), IL-6 and TNF-α, a meta-analysis using a random-effects model was used to calculate the pooled effects (CRD42021252603)., Results: Thirty-one RCT met the inclusion criteria and were included in the systematic review and meta-analysis. A significant reduction of circulating IL-6 levels following whey protein [Mean Difference (MD): -0·79, 95 % CI: -1·15, -0·42, I 2 = 96 %] and TNF-α levels following soy protein supplementation (MD: -0·16, 95 % CI: -0·26, -0·05, I 2 = 68 %) was observed. The addition of soy isoflavones exerted a further decline in circulating TNF-α levels (MD: -0·20, 95 % CI: -0·31, -0·08, I 2 = 34 %). According to subgroup analysis, whey protein led to a statistically significant decrease in circulating IL-6 levels in individuals with sarcopenia and pre-frailty (MD: -0·98, 95 % CI: -1·56, -0·39, I 2 = 0 %). These findings may be dependent on participant characteristics and treatment duration., Conclusions: These data support that whey and soy protein supplementation elicit anti-inflammatory effects by reducing circulating IL-6 and TNF-α levels, respectively. This effect may be enhanced by soy isoflavones and may be more prominent in individuals with sarcopenia.

Introduction: Empathy is an interpersonal experience that enables understanding of other's emotions and can lead to altruistic behavior such as blood donation. Cognitive theories of empathy refer to selective attention as one of its cognitive dimensions. The current study examined if individuals who engage in altruistic behavior are characterized by a distinct pattern of selective attention to observation of pain in others., Methods: We recruited 50 volunteer blood donors. Half (n = 25) of the volunteers donated for a self-declared altruistic reason, and the other half of the volunteers donated blood for a health-related reason. We assessed the individuals' self-reported empathy with the Interpersonal Reactivity Index (IRI). We then measured the individuals' selective attention toward faces expressing pain in a pictorial dot-probe task., Results: Consistent with the proposed hypothesis, participants who donated blood out of altruism reported significantly higher empathic concern on the IRI than those who donated blood for a health-related reason. The altruistic donors also showed significantly greater selective attention toward facial expressions of pain. Moreover, among all donors, self-report empathic concern on the IRI was significantly correlated with greater selective attention toward faces expressing pain., Discussion: These findings suggest that altruistic individuals not only show higher levels of empathy, but also attend more to the pain of others. Limitations, implications, and suggestions for future research are discussed., (© 2022 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: Depression, anxiety, and stress are common mental problems. The aim of this cross-sectional study was to investigate the association between two indexes that measure postprandial insulin response to different food, dietary insulin index (DII) and insulin load (DIL), with psychological disorders., Method: Participants (n = 10,000) aged 20-69 were randomly selected from 200 clusters in Yazd from the recruitment phase of the Yazd Health Study. The dietary intake of participants was collected by a reliable and validated food frequency questionnaire (FFQ) consisting of 178 food items. DII and DIL were calculated from the FFQ data using previously published reference values. To assess psychological disorders an Iranian validated short version of a self-reported questionnaire (Depression Anxiety Stress Scales 21 [DASS21]) was used., Results: No significant association was observed between DIL and DII with odds of depression or anxiety using crude or adjusted models. However, individuals in the highest quartiles of DIL had the lowest odds of stress (OR: 0.69; 95% CI 0.48-1.01, P-trend = 0.047). This association remained significant after adjustment for potential confounders in model II including marital status, smoking, education, job status, salt intake, and multi-vitamin supplement use (OR: 0.38; 95% CI 0.16-0.91, P-trend = 0.039) and the third and final model which is further adjusted for BMI (OR: 0.39; 95% CI 0.16-0.91, P-trend = 0.041)., Conclusion: Overall, consumption of foods with higher DII as well as DIL were associated with lower stress scores; however, no significant relationship was observed between DII or DIL with respective depression or anxiety scores., (© 2022. The Author(s).)

Worldwide type 2 diabetes (T2D) prevalence is increasing dramatically. The present study aimed to evaluate the association between dietary habits and T2D in an Iranian adult population using a cross-sectional analysis of the Shahedieh cohort study. Participants were adults aged 35-70 years ( n 9261) from Zarch and Shahedieh, Yazd, Iran, who attended the baseline phase of the Shahedieh cohort study. Dietary habits including meal frequency, fried-food consumption, adding salt to prepared meals and grilled-food consumption were assessed by a standard questionnaire. T2D was defined as fasting plasma glucose (FPG) ≥126 mg/dl according to the American Diabetes Association. Multiple logistic regression assessed the association between dietary habits and T2D. Individuals who consumed a meal more than six times per day compared to three times per day had greater odds for T2D (OR 2⋅503, 95 % CI 1⋅651, 3⋅793). These associations remained significant in a fully adjusted model. There was a significant association between greater intakes of fried foods and prevalence of T2D (OR 1⋅294, 95 % CI 1⋅004, 1⋅668) in the adjusted model. No significant associations were observed between other dietary habits (adding salt to prepared meals and grilled-food consumption) and odds of T2D in all crude and adjusted models. In conclusion, we have highlighted the association between meal and fried-food consumption frequencies with risk of T2D. Large longitudinal studies in different ethnicities are needed to confirm these associations., (© The Author(s) 2022.)

High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation.

Aims: Statin intolerance (SI) represents a significant public health problem for which precise estimates of prevalence are needed. Statin intolerance remains an important clinical challenge, and it is associated with an increased risk of cardiovascular events. This meta-analysis estimates the overall prevalence of SI, the prevalence according to different diagnostic criteria and in different disease settings, and identifies possible risk factors/conditions that might increase the risk of SI., Methods and Results: We searched several databases up to 31 May 2021, for studies that reported the prevalence of SI. The primary endpoint was overall prevalence and prevalence according to a range of diagnostic criteria [National Lipid Association (NLA), International Lipid Expert Panel (ILEP), and European Atherosclerosis Society (EAS)] and in different disease settings. The secondary endpoint was to identify possible risk factors for SI. A random-effects model was applied to estimate the overall pooled prevalence. A total of 176 studies [112 randomized controlled trials (RCTs); 64 cohort studies] with 4 143 517 patients were ultimately included in the analysis. The overall prevalence of SI was 9.1% (95% confidence interval 8.0-10%). The prevalence was similar when defined using NLA, ILEP, and EAS criteria [7.0% (6.0-8.0%), 6.7% (5.0-8.0%), 5.9% (4.0-7.0%), respectively]. The prevalence of SI in RCTs was significantly lower compared with cohort studies [4.9% (4.0-6.0%) vs. 17% (14-19%)]. The prevalence of SI in studies including both primary and secondary prevention patients was much higher than when primary or secondary prevention patients were analysed separately [18% (14-21%), 8.2% (6.0-10%), 9.1% (6.0-11%), respectively]. Statin lipid solubility did not affect the prevalence of SI [4.0% (2.0-5.0%) vs. 5.0% (4.0-6.0%)]. Age [odds ratio (OR) 1.33, P = 0.04], female gender (OR 1.47, P = 0.007), Asian and Black race (P < 0.05 for both), obesity (OR 1.30, P = 0.02), diabetes mellitus (OR 1.26, P = 0.02), hypothyroidism (OR 1.37, P = 0.01), chronic liver, and renal failure (P < 0.05 for both) were significantly associated with SI in the meta-regression model. Antiarrhythmic agents, calcium channel blockers, alcohol use, and increased statin dose were also associated with a higher risk of SI., Conclusion: Based on the present analysis of >4 million patients, the prevalence of SI is low when diagnosed according to international definitions. These results support the concept that the prevalence of complete SI might often be overestimated and highlight the need for the careful assessment of patients with potential symptoms related to SI., Competing Interests: Conflict of interest: P.E.P. has received honoraria and/or travel reimbursement for events sponsored by AKCEA, Amgen, AMRYT, Link Medical, Mylan, Napp, Sanofi; D.P.M. has given talks, acted as a consultant, or attended conferences sponsored by Amgen and Novo Nordisk; P.P.T.: speaker for Amgen, Esperion, Merck, Novo Nordisk; consultant to Amarin, Amgen, Kowa, Merck, Resverlogix, and Theravance; Ž.R. has given talks sponsored by Sanofi-Aventis and Novartis; M.B.: speakers bureau: Amgen, Herbapol, Kogen, KRKA, Polpharma, Mylan/Viatris, Novartis, Novo Nordisk, Sanofi-Aventis, Teva, Zentiva; consultant to Abbott Vascular, Amgen, Daichii Sankyo, Esperion, FreiaPharmaceuticals, Novartis, Polfarmex, Sanofi-Aventis; Grants from Amgen, Mylan/Viatris, Sanofi, and Valeant; CMO at Nomi Biotech Corporation; all other authors have no conflict of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Individuals with discordantly high apoB to LDL-cholesterol levels carry a higher risk of atherosclerotic CVD compared with those with average or discordantly low apoB to LDL-cholesterol. We aimed to determine associations between apoB and LDL-cholesterol discordance in relation to nutrient patterns (NP) using National Health and Nutrition Examination Survey data. Participants were grouped by established LDL-cholesterol and apoB cut-offs (Group 1: low apoB/low LDL-cholesterol, Group 2: low apoB/high LDL-cholesterol, Group 3: high apoB/low LDL-cholesterol, Group 4: high apoB/high LDL-cholesterol). Principle component analysis was used to define NP. Machine learning (ML) and structural equation models were applied to assess associations of nutrient intake with apoB/LDL-cholesterol discordance using the combined effects of apoB and LDL-cholesterol. Three NP explained 63·2 % of variance in nutrient consumption. These consisted of NP1 rich in SFA, carbohydrate and vitamins, NP2 high in fibre, minerals, vitamins and PUFA and NP3 rich in dietary cholesterol, protein and Na. The discordantly high apoB to LDL-cholesterol group had the highest consumption of the NP1 and the lowest consumption of the NP2. ML showed nutrients that had the greatest unfavourable dietary contribution to individuals with discordantly high apoB to LDL-cholesterol were total fat, SFA and thiamine and the greatest favourable contributions were MUFA, folate, fibre and Se. Individuals with discordantly high apoB in relation to LDL-cholesterol had greater adherence to NP1, whereas those with lower levels of apoB, irrespective of LDL-cholesterol, were more likely to consume NP3.

Dyslipidemia has been linked to breast cancer incidence. The aim of the present meta-analysis was to further investigate the relationship between the serum lipid profile and breast cancer risk. Databases such as PubMed, EMBASE, and Web of Sciences were searched up to the end of January 2021 using certain MeSH and non-MeSH keywords and combinations to extract related published articles. Twenty-six prospective studies involving 1,628,871 women, of whom 36,590 were diagnosed with breast cancer during the follow-up period met the inclusion criteria. A negative and significant association was found between the HDL-C level and the risk of breast cancer (relative risk (RR): 0.85, 95% CI: 0.72-0.99, I 2 : 67.6%, p = 0.04). In contrast, TG (RR: 1.02, 95% CI: 0.91-1.13, I 2 : 54.2%, p = 0.79), total cholesterol (TC) (RR: 0.98, 95% CI: 0.90-1.06, I 2 : 67.2%, p = 0.57), apolipoprotein A (ApoA) (RR: 0.96, 95% CI: 0.70-1.30, I 2 : 83.5%, p = 0.78) and LDL-C (RR: 0.93, 95% CI: 0.79-1.09, I 2 : 0%, p = 0.386) were not associated with breast cancer development. In studies adjusting for hormone use and physical activity, breast cancer risk was positively correlated with TC (RR: 1.05, 95% CI: 1.01-1.10). Similarly, TG was significantly related to breast cancer development after adjustment for baseline lipids (RR: 0.92, 95% CI: 0.85-0.99) and race (any races mentioned in each study) (RR: 1.80, 95% CI: 1.22-2.65). In the present meta-analysis, HDL-C was inversely related to breast cancer risk. Overall, data on the links between lipids and breast cancer are conflicting. However, there is increasing evidence that low HDL-C is related to an increased risk for this type of malignancy.

Chronic systemic inflammation is a risk factor for cardiovascular (CV) disease (CVD). Whether this relationship extends to subclinical inflammation, quantified by values of circulating markers associated with inflammation in the high range of the normal interval, remains debatable. This narrative review evaluates evidence exploring this relationship. A review of pharmacological and non-pharmacological interventions, including diet and lifestyle strategies, supplements, nutraceuticals, and other natural substances aimed at reducing inflammation was also conducted, since few reviews have synthesized this literature. PubMed and EMBASE were used to search the literature and several well-studied triggers of inflammation [oxidized LDL, Lp(a), as well as C-reactive protein (CRP)/high-sensitivity CRP (hs-CRP)] were included to increase sensitivity and address the lack of existing reviews summarizing their influence in the context of inflammation. All resulting references were assessed. Overall, there is good data supporting associations between circulating hs-CRP and CV outcomes. However, the same was not seen in studies evaluating triggers of inflammation, such as oxidized LDL or Lp(a). There is also insufficient evidence showing treatments to target inflammation and lead to reductions in hs-CRP result in improvements in CV outcomes, particularly in those with normal baseline levels of hs-CRP. Regarding pharmacological interventions, statins, bempedoic acid, and apabetalone significantly reduce circulating hs-CRP, unlike PCSK-9 inhibitors. A variety of natural substances and vitamins were also evaluated and none reduced hs-CRP. Regarding non-pharmacological interventions, weight loss was strongly associated with reductions in circulating hs-CRP, whereas various dietary interventions and exercise regimens were not, unless accompanied by weight loss., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Blood pressure (BP) control is a key target for interventions to reduce cognitive decline. This cross-sectional study explored associations between objective (24-hour urine excretion) and subjective (food frequency questionnaire [FFQ]) measures of dietary sodium and nitrate intakes with cognitive function and resting BP in the InCHIANTI cohort. Baseline data from 989 participants aged >50 years were included. In fully adjusted models, participants with concurrent high nitrate and low sodium (Odds Ratio (OR)=0.49, 95%CI 0.32-0.76, p  = 0.001) and high nitrate and high sodium (OR = 0.49, 95%CI 0.32-0.77, p  = 0.002) 24-hour urinary concentrations had lower odds of high BP than participants with low nitrate and high sodium concentrations. We found no significant associations between sodium and nitrate intakes (24-hour urinary concentrations and FFQ) and poor cognitive performance. Urinary nitrate excretion was associated with lower BP and results appeared to be independent of sodium intake. Further analyses in longitudinal studies are required to substantiate these findings.

The study of moral judgements often centres on moral dilemmas in which options consistent with deontological perspectives (that is, emphasizing rules, individual rights and duties) are in conflict with options consistent with utilitarian judgements (that is, following the greater good based on consequences). Greene et al. (2009) showed that psychological and situational factors (for example, the intent of the agent or the presence of physical contact between the agent and the victim) can play an important role in moral dilemma judgements (for example, the trolley problem). Our knowledge is limited concerning both the universality of these effects outside the United States and the impact of culture on the situational and psychological factors affecting moral judgements. Thus, we empirically tested the universality of the effects of intent and personal force on moral dilemma judgements by replicating the experiments of Greene et al. in 45 countries from all inhabited continents. We found that personal force and its interaction with intention exert influence on moral judgements in the US and Western cultural clusters, replicating and expanding the original findings. Moreover, the personal force effect was present in all cultural clusters, suggesting it is culturally universal. The evidence for the cultural universality of the interaction effect was inconclusive in the Eastern and Southern cultural clusters (depending on exclusion criteria). We found no strong association between collectivism/individualism and moral dilemma judgements., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Objective: This cross-sectional study aimed to study the prevalence rate of psychiatric disorders in children and adolescents in Khuzestan province., Materials & Methods: A community sample consisting of 1028 (51.6% female) children and adolescents aged 6-18 years was selected using a multistage cluster sampling method. Data were gathered using the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL) and a demographic questionnaire (i.e., gender, age, level of education, place of residence, parent's education, and parent's Job)., Results: Nearly 22.6% (22.3% of boys and 23% of girls) of all participants suffered from at least one psychiatric disorder. There was no significant difference in the prevalence of psychiatric disorders based on gender, age, father's education, mother's education, mother's job, and father's job (all p>0.05). Psychiatric disorders were significantly more prevalent among children and adolescents in urban areas compared to rural places (2.9% vs. 8.1; p<0.001). The most prevalent category was anxiety disorders (15%). Also, the most common disorders were specific phobia (7%), separation anxiety disorder (6.3%), and enuresis (5.2%). The most common comorbid disorders were mood disorders and anxiety disorders (56.3%), followed by anxiety disorders and elimination disorders (32.1%)., Discussion: Psychiatric conditions are prevalent in children and adolescents living in Khuzestanian. The study's findings have important implications for providing effective psychiatric services., Competing Interests: the authors declare no conflict of interest., (© 2022 The Authors.)

Statin intolerance is a clinical syndrome whereby adverse effects (AEs) associated with statin therapy [most commonly statin-associated muscle symptoms (SAMS)] result in the discontinuation of therapy and consequently increase the risk of adverse cardiovascular outcomes. However, complete statin intolerance occurs in only a small minority of treated patients (estimated prevalence of only 3-5%). Many perceived AEs are misattributed (e.g. physical musculoskeletal injury and inflammatory myopathies), and subjective symptoms occur as a result of the fact that patients expect them to do so when taking medicines (the nocebo/drucebo effect)-what might be truth even for over 50% of all patients with muscle weakness/pain. Clear guidance is necessary to enable the optimal management of plasma in real-world clinical practice in patients who experience subjective AEs. In this Position Paper of the International Lipid Expert Panel (ILEP), we present a step-by-step patient-centred approach to the identification and management of SAMS with a particular focus on strategies to prevent and manage the nocebo/drucebo effect and to improve long-term compliance with lipid-lowering therapy., (© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Background: The hepatoprotective effects of phytochemicals are controversial. A dietary phytochemical index (DPI) has been suggested as an alternative method for quantifying the phytochemical content of foods., Aim: To assess the DPI in relation to liver function tests among a representative sample of Iranian adults., Methods: A total of 5111 participants aged 35-70 years old were included in this cross-sectional study by a multistage cluster random sampling method. Dietary intakes were collected by a validated and reliable food frequency questionnaire with 121 items. DPI was calculated by the percent of daily energy intake taken from phytochemical-rich foods. Fasting serum concentrations of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) were determined. Linear regression was used to investigate the association between DPI and levels of liver enzymes using crude and adjusted models., Results: There was an inverse association between DPI score and serum ALP in the crude model (β = -0.05; P < 0.001). This association remained significant after adjustment for body mass index, age, smoking, energy intake, history of diabetes, and education (β = -0.03; P = 0.01). No significant associations were found between DPI score and serum levels of AST, ALT, and GGT. The individuals with the highest DPI scores consumed significantly higher amounts of fruits, vegetables, legumes, nuts, and cereals, yet were shown to have significantly higher serum total cholesterol and low-density lipoprotein cholesterol, as well as several other metabolic abnormalities., Conclusion: Higher adherence to phytochemical-rich foods was associated with lower levels of ALP, but no change in other liver enzymes. Those with higher DPI scores also consumed food items associated with a healthier overall dietary pattern; however, they also presented several unexpected metabolic derangements. Additional randomised trials are needed to better determine the effects of phytochemical-rich foods on liver function., Competing Interests: Conflict-of-interest statement: The authors know of no conflicts of interest associated with this publication, and there has been no significant financial support for this work that could have influenced its outcome., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Ultra-processed foods have been associated with increased risk of chronic disease, poor overall health and psychological outcomes. This study explored the association of ultra-processed foods with quality of life in adolescent girls from northeastern Iran. In an interdisciplinary cross-sectional study, n = 733 adolescent girls were recruited by random cluster sampling. Assessments were completed for demographics, physical activity, anthropometric and biochemical parameters, psychological health and dietary intake. The participants were categorized into quartiles of ultra-processed food intake, and multivariable logistic regression was used in several models to investigate the association between ultra-processed food intake and psychological health. The mean age of the participants was 14 years. There were no significant differences in participant demographics for the quartiles of ultra-processed food intake including weight, waist-hip ratio, waist circumference, depression, insomnia and cardiometabolic markers related to cardiovascular disease risk. Adjusted logistic regression showed participants in the highest category of ultra-processed food consumption had an increased likelihood of reduced quality of life (OR: 1.87, 95% CI: 1.13-3.11), with a greater chance for insomnia (OR: 4.04, 95% CI: 1.83-8.94) across all models. However, no significant associations were observed between consumption of ultra-processed foods and daytime sleepiness. We highlight the association between ultra-processed food consumption and poor quality of life and insomnia amongst adolescent girls. Large longitudinal integrated public health studies in different ethnicities are needed to confirm these associations and evaluate their possible impact for optimizing health promotion programs.

Background: Psychological disorders including depression, anxiety, and stress comprise a huge public health problem. The aim of this cross-sectional study is to assess the relationship between dietary glycemic index (DGI) and glycemic load (DGL) and mental disorders., Method: Participants (n = 10,000) aged 20-69 were randomly selected from 200 clusters in Yazd from the recruitment phase of Yazd Health Study. The dietary intake of study participants was collected by a reliable and validated food frequency questionnaire consisting of 178 food items. DGI and DGL were calculated from the FFQ data using previously published reference values. To assess psychological disorders an Iranian validated short version of a self-reported questionnaire Depression Anxiety Stress Scales 21 was used., Results: There were no significant associations between DGI and DGL with odds of depression or anxiety in crude and adjusted models. However, individuals in the highest quartiles of DGL had the lowest odds of stress (OR: 0.69; 95% CI 0.47-1, P-trend = 0.023). This association remained significant after adjustment for potential confounding variables in model I (OR: 0.45; 95% CI 0.22-0.9, P-trend = 0.023), model II (OR: 0.46; 95% CI 0.22-0.96, P-trend = 0.039) and model III (OR: 0.46; 95% CI 0.22-0.96, P-trend = 0.042)., Conclusion: In conclusion, consumption of foods with higher GL was associated with lower odds of stress; however, no significant association was found between DGI or DGL and risk of depression and anxiety. Performing further studies with longitudinal design is suggested to confirm these results., (© 2022. The Author(s).)

Background: Insomnia is associated with a poor quality of life and increased risk of somatic and social problems. The aim of current study was to investigate the relationship between dietary behaviors and insomnia in Iranian adolescent girls., Methods: This cross-sectional study was performed among 988 girls aged 12-18 years. A questionnaire was used to determine dietary behaviors in nine domains. To assess insomnia, a validated Iranian version of the Insomnia Severity Index was applied. Multivariable logistic regression examined the association between dietary behaviors and insomnia in crude and adjusted models., Results: Highest adherence to regular meal consumption was related to the lowest odds of insomnia (odds ratio [OR]: 0.44, 95% confidence interval [CI]: 0.24-0.81). Compared with individuals who consumed breakfast never or once a week, those who always consumed breakfast had a lower likelihood of insomnia (OR: 0.56, 95% CI: 0.36-0.88). These associations remained significant in all adjusted models. Subjects who ate spicy food every day had 4.73 times greater odds of insomnia than individuals who never ate spicy food (OR: 4.73, 95% CI: 1.09-20.56). After controlling for age, menstruation, parent death, parents' divorce and parents' (mother and father) employment status, this relationship remained (OR: 4.59, 95% CI: 1.05-20.10); however, the association was no longer significant after controlling for the other covariates. No significant relationship was found between other dietary habits and insomnia for the unadjusted or adjusted models., Conclusion: Lowest rates of insomnia were found among participants who had the lowest frequency of eating spicy foods and the highest frequency of eating breakfast and eating regular meals. Further prospective studies are required to confirm these findings., (Copyright © 2021 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.)

Clinical trials have suggested that increased 25-hydroxyvitamin D (25(OH)D) has positive effect on hand grip strength. This Mendelian randomisation (MR) was implemented using summary-level data from the largest genome-wide association studies on vitamin D (n = 73,699) and hand grip strength. Inverse variance weighted method (IVW) was used to estimate the causal estimates. Weighted median (WM)-based method, MR-Egger and leave-one-out were applied as sensitivity analysis. Results showed that genetically higher-serum 25(OH)D levels had a positive effect on both right hand grip (IVW = Beta: 0.038, P = 0.030) and left hand grip (IVW = Beta: 0.034, P = 0.036). There was a low likelihood (statistically insignificant) of heterogeneity and pleiotropy, and the observed associations were not driven by single single-nucleotide polymorphisms. Furthermore, MR pleiotropy residual sum and outlier did not highlight any outliers. In conclusion, our results highlighted the causal and beneficial effect of serum 25(OH) D on right- and left-hand grip strengths., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Dietary macronutrient composition influences both hepatic function and aging. Previous work suggested that longevity and hepatic gene expression levels were highly responsive to dietary protein, but almost unaffected by other macronutrients. In contrast, we found expression of 4005, 4232, and 4292 genes in the livers of mice were significantly associated with changes in dietary protein (5%-30%), fat (20%-60%), and carbohydrate (10%-75%), respectively. More genes in aging-related pathways (notably mTOR, IGF-1, and NF-kappaB) had significant correlations with dietary fat intake than protein and carbohydrate intake, and the pattern of gene expression changes in relation to dietary fat intake was in the opposite direction to the effect of graded levels of caloric restriction consistent with dietary fat having a negative impact on aging. We found 732, 808, and 995 serum metabolites were significantly correlated with dietary protein (5%-30%), fat (8.3%-80%), and carbohydrate (10%-80%) contents, respectively. Metabolomics pathway analysis revealed sphingosine-1-phosphate signaling was the significantly affected pathway by dietary fat content which has also been identified as significant changed metabolic pathway in the previous caloric restriction study. Our results suggest dietary fat has major impact on aging-related gene and metabolic pathways compared with other macronutrients., (© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Cognitive theories of eating disorders implicate Attentional Bias (AB) towards food-related information in the development and maintenance of eating disorders. Empirical evidence for this proposal, however, has been inconsistent, and the measures used to examine AB to food-related stimuli typically showed poor reliability. The aim of the current study was twofold. Firstly, we aimed to examine the psychometric properties of a newly devised eye-tracking task for the assessment of AB in the context of eating disorders. Secondly, we examined the role of Eating Disorder-specific (ED-specific) rumination as a potential moderator of the association between attentional bias to food images and eating disorder symptoms. One hundred and three female students were recruited and completed an eye-tracking task comprising 21 matrices that each contained 8 low-calorie and 8 high-calorie food images. Each matrix was presented for 6 s. First fixation location, first fixation latency, and total dwell time were assessed for low and high-calorie food images and the dwell-time based AB measure showed good reliability based on Cronbach's alpha, McDonald's Omega, and split-half method. In addition, the results revealed that the ED-specific rumination plays the hypothesized moderating role. Specifically, while participants with high levels of ED-specific rumination exhibited a positive association between AB to high-calorie foods and eating disorder symptoms, this association was not present among participants with lower levels of ED-specific rumination. The employed free-viewing task seems a reliable measure of AB to food-related stimuli, and the moderation analysis emphasizes the critical role of ED-specific rumination for eating disorder symptoms. Implications, limitations, and directions for future research are discussed., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Polyunsaturated fatty acid (PUFA) intake is generally associated with better renal function, while the association of monounsaturated fatty acids (MUFAs) remains unconfirmed. Mendelian randomization (MR) analysis was used to obtain unconfounded estimates of the causal association of dietary intake and genetically determined serum PUFA and MUFA levels with measures of renal function. Data from participants of the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2010 were used. Data from the largest genome-wide association studies (GWAS) on MUFAs, PUFAs, eGFR, and chronic kidney disease (CKD) were analysed for the entire sample. A total of 16,025 participants were included. eGFR improved across increasing quartiles of total PUFA intake from 86.3 ± 0.5 (Q1) to 96.2 ± 0.5 mL/min/1.73 m² (Q4), (p < 0.001). Conversely, there was no association between MUFA intake and measures of renal function (all p > 0.21). In multivariable models, the top quartile of PUFA intake had a 21% lower risk for CKD, but there was no significant association between CKD risk and MUFA intake. Genetically determined serum MUFA (heptadecenoate (17:1), myristoleic acid (14:1), and palmitoleic acid (16:1)) and PUFA (α-linolenic acid and eicosapentaenoic acid) concentrations had no significant association with eGFR and CKD risk. Additionally, no association was found in the analyses stratified by diabetes status. Higher dietary PUFA intake is associated with lower risk of CKD, while there was no association with serum levels of MUFAs or PUFAs. Additional studies including clinical trials are warranted.

Background: Increased protein intake is suggested as a strategy to slow or reverse the loss of muscle mass and strength observed in sarcopenia, but results from studies that directly tested this possibility have been inconsistent., Objectives: We assessed the evidence on the effects of whole protein supplementation or higher-protein diets, without the use of amino acids or supplements known to stimulate hypertrophy, alone or in combination with resistance exercise (RE) interventions, on lean body mass (LBM) and strength in older adults., Methods: A systematic search was conducted using PubMed, Medline, Web of Science, and Cochrane CENTRAL databases from January 1990 to July 2021. Randomized controlled trials that assessed the effects of protein supplementation and/or higher-protein dietary interventions in older adults (mean age ≥50 y) on total LBM, appendicular lean mass (ALM), and handgrip (HG) and knee extension (KE) strength were included., Results: Twenty-eight studies were identified. In pooled analysis, compared with lower protein controls, protein supplementation did not have a significant positive effect on total LBM [weighted mean difference in change (WMD): 0.34; 95% CI: -0.21, 0.89; I2 = 90.01%], ALM (WMD: 0.4; 95% CI: -0.01, 0.81; I2 = 90.38%), HG strength (WMD: 0.69; 95% CI: -0.69, 2.06; I2 = 94.52%), or KE strength (WMD: 1.88; 95% CI: -0.6, 4.35; I2 = 95.35%). However, in interventions that used also RE, statistically significant positive effects of protein were observed for ALM (WMD: 0.54; 95% CI: 0.03, 1.05; I2 = 89.76%) and HG (WMD: 1.71; 95% CI: 0.12, 3.30; I2 = 88.71%). Meta-regression revealed no significant association between age, per-meal protein dose, duration, and baseline protein intake with change in any outcome. Subgroup analysis revealed the statistically significant effects on ALM occurred only in sarcopenic/frail populations (WMD: 0.88; 95% CI: 0.51, 1.25; I2 = 79.0%). Most studies (n = 22) had some risk of bias., Conclusions: In older adults performing RE, increased protein intake leads to greater ALM and HG strength compared with lower protein controls. Without RE, protein has no additional benefit on changes in total LBM, ALM, or HG strength., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

The blood level of lipids, apolipoproteins, and lipid ratios are important predictors of some chronic diseases. However, their association with cardiometabolic multimorbidity (CMM) is less known. We evaluated a wide range of lipid profiles and lipid ratios, including low-density lipoprotein-cholesterol (LDL-C), very-low-density lipoprotein-cholesterol (VLDL-C), high-density lipoprotein-cholesterol (HDL-C), and apoA1 and B, as well triglyceride and total cholesterol with risk of incident CMM. In 1728 men aged 52.5 ± 5.2 years from the Kuopio Ischaemic Heart Disease were included in this study. We defined CMM as coexisting of two or more of stroke, type 2 diabetes mellitus (T2D), coronary heart disease (CHD). A Cox proportional hazard regression method was applied to evaluate the risk of CMM against the exposures. During the mean follow-up of 22.4 years, 335 men suffered from CMM conditions. Higher serum triglyceride and VLDL concentrations were associated with a higher risk of coexisting T2D-CHD (HRs 1.99 (95% CI, 1.12-3.53) and HRs 1.79 (95% CI, 1.04-3.11), respectively. Whereas higher HDL was associated with lower incident [HRs 0.49 (95% CI, 0.40-1.00)]. The HRs for coexisting T2D-CHD was 2.02 (95% CI, 1.01-3.07) for total cholesterol/HDL-C, 1.85 (95% CI, 1.04-3.29) for triglyceride/HDL-C, 1.69 (95% CI, 1.01-2.31) for Non-HDL-C/HDL-C, and 1.89 (95% CI, 1.03-2.46) for apoB/apoA1. In contrast, serum LDL-C/apoB ratios were inversely associated with the risk of coexisting T2D-CHD [HRs 0.50 (95% CI, 0.28-0.90)]. No associations were observed between our exposures and other CMM conditions. In conclusion, elevated triglyceride, VLDL-C, total cholesterol/HDL-C, TG/HDL-C, apoB/apoA1 as well as lower LDL-C/apoB were independently associated with the higher risk of T2D-CHD coexistence., (© 2022 The Authors. Lipids published by Wiley Periodicals LLC on behalf of AOCS.)

Background and Aims: While low-density lipoprotein cholesterol (LDL-C) is a good predictor of atherosclerotic cardiovascular disease, apolipoprotein B (ApoB) is superior when the two markers are discordant. We aimed to determine the impact of adiposity, diet and inflammation upon ApoB and LDL-C discordance., Methods and Results: Machine learning (ML) and structural equation models (SEMs) were applied to the National Health and Nutrition Examination Survey to investigate cardiometabolic and dietary factors when LDL-C and ApoB are concordant/discordant. Mendelian randomisation (MR) determined whether adiposity and inflammation exposures were causal of elevated/decreased LDL-C and/or ApoB. ML showed body mass index (BMI), dietary saturated fatty acids (SFA), dietary fibre, serum C-reactive protein (CRP) and uric acid were the most strongly associated variables (R 2  = 0.70) in those with low LDL-C and high ApoB. SEMs revealed that fibre (b = -0.42, p = 0.001) and SFA (b = 0.28, p = 0.014) had a significant association with our outcome (joined effect of ApoB and LDL-C). BMI (b = 0.65, p = 0.001), fibre (b = -0.24, p = 0.014) and SFA (b = 0.26, p = 0.032) had significant associations with CRP. MR analysis showed genetically higher body fat percentage had a significant causal effect on ApoB (Inverse variance weighted (IVW) = Beta: 0.172, p = 0.0001) but not LDL-C (IVW = Beta: 0.006, p = 0.845)., Conclusion: Our data show increased discordance between ApoB and LDL-C is associated with cardiometabolic, clinical and dietary abnormalities and that body fat percentage is causal of elevated ApoB., Competing Interests: Declaration of competing interest None declared., (Copyright © 2021 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. All rights reserved.)

Sarcopenic obesity (SO) is characterised by the concurrent presence of sarcopenia and excess adiposity. Telomere shortening has been associated with sarcopenia and obesity alone but the association between SO and telomere length (TL) has not been investigated. This study aimed to investigate SO and TL in an adult population. Data were from 5397 individuals (mean age = 44.7 years, 51.3% male) enrolled in the National Health and Nutrition Examination Survey. Body composition (BC) was assessed by Dual Energy X-Ray Absorptiometry. Two models were used to assess SO: a BC model including four phenotypes derived from the combination of high or low adiposity and muscle mass; and, a truncal fat mass to appendicular skeletal mass ratio (TrFM/ASM). TL was assessed using quantitative polymerase chain reaction and expressed as base pairs. The mean TL, relative to the reference DNA, was calculated and expressed as the mean T/S ratio. A General Linear Model was applied to determine associations between TL for SO. In adjusted analysis, only individuals with SO, defined as the presence of high adiposity-low muscle mass (four-phenotype model), had significantly shorter telomeres (p = 0.05) than the reference group (i.e. low adiposity-high muscle mass), with a mean T/S ratio of 1.02 (95%CI: 0.98-1.05) compared to 1.05 (95%CI: 1.01-1.09), respectively. TrFM/ASM was not associated with TL. Preliminary findings suggest that sarcopenia and obesity may act synergistically to shorten telomeres., (© 2021. The Author(s).)

Introduction: The impact of low-density lipoprotein cholesterol (LDL-C) on the risk of different types of strokes is unclear. Therefore, we systematically evaluated the impact of LDL-C levels (cohort studies) and lipid-lowering agents (LLAs) (randomized controlled trials) on the different types of stroke., Material and Methods: PubMed, SCOPUS, Web of Science and Google Scholar were searched up to 1 st September 2019. The DerSimonian-Laird method and generic inverse variance methods were used for quantitative data synthesis. The leave-one-out method was performed as sensitivity analysis. Trial sequential analysis (TSA) was used to evaluate the optimal sample size to detect a 35% reduction in outcomes after administration of LLAs., Results: Participants in the highest category of LDL-C had a lower risk of hemorrhagic stroke (RR = 0.91, 95% CI: 0.85-0.98, I 2 = 0%) compared with the lowest category of LDL-C. Subjects with the highest category of LDL-C had a higher risk of ischemic stroke (RR = 1.11, 95% CI: 1.07-1.14, I 2 = 0%) compared to the lowest LDL-C category. LLAs decreased the risk of all types of strokes for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.88, 95% CI: 0.80-0.96, absolute risk reduction (ARR): 0.7%, number needed to treat (NNT): 143, I 2 = 53%, n = 13). Statin therapy decreased the risk of all strokes (RR = 0.88, 95% CI: 0.80-0.97, ARR = 0.6%, NNT = 167, I 2 = 56%). With regard to ischemic stroke only, LLAs decreased the risk of ischemic stroke for those who achieved LDL-C < 1.8 mmol/l (< 70 mg/dl; RR = 0.75, 95% CI: 0.67-0.83, ARR = 1.3%, NNT = 77, I 2 = 0%); the same was observed for statins (RR = 0.76, 95% CI: 0.69-0.84, ARR = 1.3%, NNT = 77, I 2 = 32%). TSA indicated that both benefit boundaries and optimal sample size were reached. There was no significant effect of LLAs regardless of the achieved level of LDL-C on the risk of hemorrhagic stroke; however, TSA indicated that further studies are needed to settle the question and most of the effects were subject to high levels of heterogeneity., Conclusions: Our study sheds light on the debatable association between low LDL-C and different type of strokes. This information can help determine the optimal LDL-C range for stroke prevention, and help plan future LLA studies., Competing Interests: MB has received research grant(s)/support from Amgen, Sanofi Valeant, Viatris, and has served as a consultant for Abbott Medical, Amgen, Daichii Sankyo, Esperion, Herbapol, Kogen, KRKA, Polfarmex, Polpharma, Roche Diagnostics, Sanofi-Aventis, Servier, Teva, Zentiva; he is CMO at Nomi Biotech Corporation; DPM has given talks and attended conferences sponsored by MSD, AstraZeneca and Libytec; GYHL: Consultant for Bayer/Janssen, BMS/Pfizer, Medtronic, Boehringer Ingelheim, Novartis, Verseon and Daiichi-Sankyo. Speaker for Bayer, BMS/Pfizer, Medtronic, Boehringer Ingelheim, and Daiichi-Sankyo – no fees are directly received personally. The other authors declare no conflict of interest., (Copyright: © 2022 Termedia & Banach.)